Prostate Cancer (PCa) is the most commonly diagnosed malignancy in men, and is found at autopsy in 30% of men at the age of 50, 40% of men at age 60, and almost 90% of men at age 90. Worldwide, it is the second leading cause of death due to cancer in men, accounting for between 2.1% and 15.2% of all cancer deaths. In Canada, 18,800 new PCa cases were diagnosed (26% of all new cancers in men) and 4,200 men died from this disease in 2003. In the United States, 189,000 new cases were diagnosed and 30,200 died from PCa in 2002. When diagnosed at an early stage, the disease is curable, and even at later stages treatment can be effective. Once the tumor has extended beyond the prostate, however, the risk of metastases increases. In managing patients with possible PCa, the challenges facing physicians are to: (a) diagnose clinically relevant cancers at a curable stage, (b) stage the disease accurately, (c) apply the appropriate therapy accurately to destroy cancer cells while preserving normal tissues, and (d) follow patients to assess side effects and therapy effectiveness.
Definitive diagnosis of PCa involves the detection of cancerous tissue obtained from the prostate during biopsy. Ultrasound-guided biopsy methodologies such as for the detection of prostate cancer are well-known and require needles to be inserted into the body to obtain a biopsy sample of one or more target tissue areas. Historically, these biopsy methodologies have been inaccurate. The introduction of trans-rectal ultrasound (“TRUS”) has revolutionized prostate biopsy techniques and has greatly increased the accuracy of biopsy. Widespread screening for PCa using the prostate-specific antigen (“PSA”) test has greatly increased the numbers of TRUS-guided biopsy. While TRUS-guided prostate biopsy has become a commonly-performed urological procedure, it is not without limitations and controversy. Chief among the problems facing urologists daily relates to the management of patients in whom a first set of prostate biopsies were negative for cancer. Since the prostate volume sampled by the biopsy is small and PCa is often multifocal, involving only a small volume of the prostate in the early stages of the disease, may result in a false negative biopsy. The end result is patients harboring cancer at early and curable stages. Management of these patients, as well as those diagnosed with early stage disease, has generated a great deal of debate and controversy, driving the need for improved prostate biopsy techniques to help resolve.
The controversies related to the decision of how best to manage early-stage PCa are among the most intensely debated in all of clinical medicine by medical professionals as well as concerned patients. Management options for early-stage PCa are: “watchful-waiting”, hormone therapy, surgery and radiotherapy. Since the natural history of PCa is long and many patients diagnosed with PCa are elderly, some have argued that “watchful-waiting” is appropriate. Patients with intermediate-grade and high-grade cancers, however, can have a substantial risk of early local failure if an intervention is not undertaken. Clearly, in order to provide the patient with the best and most appropriate treatment option, an accurate prostate biopsy procedure is crucial in obtaining sufficient cancerous tissue for grading if cancer is present.
Various reports have shown that the detection rate on repeat biopsy ranges between 10% to 25% (after the first biopsy was negative). Although advances in technology and understanding of the disease have produced improvements in the biopsy procedure, significant dilemmas and technical challenges clearly remain. For example, if an initial biopsy fails to detect cancer, who should undergo a repeat biopsy? How should a repeat biopsy be directed? Should the repeat (and initial) biopsy be lesion-directed, random, or based on the details of the patient's anatomy (e.g., prostate regions, volume, shape).
Worldwide, the most common indication for prostate biopsy is the presence of serum PSA levels greater than 4.1 ng/ml. Because a significant proportion of men with PSA in the 2.5 to 4.0 ng/ml range have PCa, some investigators have advocated decreasing the PSA threshold to enhance PCa detection. While early detection may increase the probability that the disease is confined to the prostate and that such patients are more likely to be free of PSA failure with improved disease-free survival after treatment, lowering the threshold significantly increases the numbers of patients treated for non-lethal PCa. Despite the ongoing debate and lack of a general consensus at this time, some centers have lowered the threshold for younger men, significantly increasing the numbers of prostate biopsies performed. As lowering this threshold results in biopsies of prostates with a small volume of cancer, improved biopsy techniques are clearly required to increase the yield on the first biopsy and improve the planning of the potentially increasing numbers of repeated biopsies.
In many cases, significant discomfort is reported during the biopsy procedure. After biopsy, common side-effects include hematuria, hematospermia and hematochezia in about a third to a half of patients. Although these are relatively minor, there is a potential for other less frequent post-biopsy morbidity including sepsis (0.2%-0.6%), urinary tract infection (0.1%-4.5%) and urinary retention (0.2%-1.2%). As a result, it is desirable to reduce the frequency of such procedures.
The optimal distribution of cores within the prostate has been studied extensively, and it has been shown that uniform biopsy approaches such as sextant methods are subject to sampling limitations in view of the wide variations in gland sizes. This issue has been explored using computer simulations of the biopsy procedure and prostate anatomy, with probability distribution of location, frequency and volume of prostate carcinoma obtained from radical prostatectomy specimens. Results from computer simulations and clinical studies, which explored different systematically distributed cores, have demonstrated that the positive biopsy yield depends on the magnitude of gland sampling. Increasing the number of biopsy cores increases the biopsy yield, and this effect is most pronounced in larger prostates. Using the same number of cores regardless of individual prostate characteristics may lead to over-sampling of small glands, and less extensive and potentially inadequate sampling of large glands.
With more men undergoing PSA testing and the potentially lowered PSA threshold for prostate biopsy, physicians commonly face the dilemma of the patient with a negative prostate biopsy who still has suspicious clinical exam or serum PSA results. With the limited informational value of a negative biopsy, and that no evidence of cancer on biopsy does not preclude the possibility of a missed cancer, patients are often required to undergo repeat biopsies when clinical suspicion exists and in cases when a positive biopsy for cancer would have therapeutic consequences. Since there are an appreciable number of men with false-negative biopsy who in fact harbor curable PCa, the medical science is faced with a difficult challenge.
Many investigators have examined the positive yields on repeated biopsies of men with elevated PSA or suspicious digital rectal exam (“DRE”) or TRUS finding. The results demonstrated that on the first biopsy, about 15% to 40% of men had PCa, about 15% to 23% of men had PCa on the second biopsy and 8% to 10% of men had PCa on the third biopsy. In some of the patients with false-negative biopsy, the cancer might be clinically insignificant, warranting no therapy, but some of these patients might benefit from detection and subsequent treatment.
Another important challenge facing physicians is in men diagnosed on biopsy to have pre-malignant lesions, i.e. high-grade prostatic intraepithelial neoplasia (“PIN”), and particularly atypical small acinar proliferation (“ASAP”). These are challenging to manage as there is a 40% to 50% chance of finding cancer on repeat biopsy with ASAP. Since co-existing cancer might be present, especially with ASAP, where the pathologist finds only a small amount of histologic “atypia” but not enough material to confidently diagnose cancer, these patients typically undergo a repeat biopsy soon after the first. In these situations, it is important to re-biopsy the same area to increase the yield. Currently, only a vague location of the abnormal findings is available, and it is not possible to be certain that the same area has been sampled on the repeat biopsy.
As a result of the increasing number of younger men with potentially early and curable PCa undergoing repeated prostate biopsy, it is therefore important not to re-biopsy the same area if the original biopsy was negative, and it is particularly important to re-biopsy the exact area if a possible abnormal area was detected on first biopsy as ASAP. Thus, improved guidance to suspicious regions of the prostate using information from other modalities is desired, as well as the locations of the cores obtained from the prostate must be known accurately to help guide the physician during the repeat biopsy, in order to help in correlating any imaging evidence of the disease and provide improved planning for the subsequent therapy.
It is, therefore, an object of the present invention to provide a novel system and method for performing a biopsy on a target volume and a computing device for planning the same.